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Crystal structure and functional analysis of Leishmania major pseudoperoxidase.

ABSTRACT: Leishmania major pseudoperoxidase (LmPP) is a recently discovered heme protein expressed by the human pathogen. Previous in vivo and in vitro studies suggest that LmPP is a crucial element of the pathogen's defense mechanism against the reactive nitrogen species peroxynitrite produced during the host immune response. To shed light on the potential mechanism of peroxynitrite detoxification, we have determined the 1.76-Å X-ray crystal structure of LmPP, revealing a striking degree of homology with heme peroxidases. The most outstanding structural feature is a Cys/His heme coordination, which corroborates previous spectroscopic and mutagenesis studies. We also used a combination of stopped-flow and electron paramagnetic spectroscopies that together suggest that peroxynitrite is not a substrate for LmPP catalysis, leaving the function of LmPP an open question.

SUBMITTER: Chreifi G

PROVIDER: S-EPMC5976444 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Crystal structure and functional analysis of Leishmania major pseudoperoxidase.

Chreifi Georges G Dejam Dillon D Poulos Thomas L TL

Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry 20170605 6

Leishmania major pseudoperoxidase (LmPP) is a recently discovered heme protein expressed by the human pathogen. Previous in vivo and in vitro studies suggest that LmPP is a crucial element of the pathogen's defense mechanism against the reactive nitrogen species peroxynitrite produced during the host immune response. To shed light on the potential mechanism of peroxynitrite detoxification, we have determined the 1.76-Å X-ray crystal structure of LmPP, revealing a striking degree of homology with ...[more]

PMID: 28584975

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| S-EPMC3091252 | biostudies-literature

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